Association of genetic variation in TLR4 and TLR9 genes with susceptibility to invasive ductal breast carcinoma.

BACKGROUND

Toll-like receptors (TLRs) are pattern recognition receptors playing a vital role in innate immunity. The genetic mutations in TLR4 and TLR9 genes may lead to altered function, contributing to cancer onset and progression. The aim of the study is to examine the association between genetic variations in the TLR4 and TLR9 genes and susceptibility to invasive ductal carcinoma (IDC).

METHODS

This study included 122 women in total; 61 had IDC and 61 were controls. The TLR4 and TLR9 genes were amplified by the PCR and sequenced through the Sanger sequencing method, followed by single nucleotide polymorphism (SNP) analysis. The chi-square test was applied, and ORs with 95% CI were calculated. A p-value < 0.05 was considered significant.

RESULTS

In the IDC group, 10 mutations were identified in TLR4 and TLR9, including six SNPs, three deletions and one insertion. In TLR4, the non-synonymous SNPs A896G and A1214T were each observed in 10% of patients, while a complete codon change (GAT > ATC) at positions 1213–1215 was found in 20%. The synonymous SNP A1029G was detected in 3%, and deletion was found in 34% of patients. TLR4 genotype distribution differed significantly among patients and controls. AAGAT was the most common haplotype. In TLR9, two SNPs, G1635A (15%) and A1759C (5%), were identified, and G1635A showed a significant association with tumor grades. The GA haplotype was most frequent. No linkage disequilibrium (LD) was found among the analyzed SNPs.

CONCLUSION

Polymorphisms in TLR4 and TLR9 are associated with an increased risk of developing IDC.